title: Inhibition of complement activation by soluble recombinant CR1 under conditions resembling those in a cardiopulmonary circuit: reduced up-regulation of CD11b and complete abrogation of binding of PMNs to the biomaterial surface.
abstract: The influence of soluble recombinant CR1 (sCR1) on complement activation, and its indirect effects on the coagulation system and cellular responses were assessed in two models for the study of blood/surface and blood/air interactions, as are encountered in e.g. cardiopulmonary bypass circuits. The concentrations of C3a and sC5b-9 and the amount of bound C3/C3 fragments were analyzed as indicators of complement activation. Thrombin-antithrombin complexes, the platelet count, surface-ATP, beta-thromboglobulin, and the expression of CD11b on leukocytes were the parameters analyzed to reflect coagulation and cellular responses. In addition, immunochemical analyses of the phenotypes of surface-bound leukocytes and platelets were performed. Recombinant sCR1, at doses ranging between 0.1-0.25 mg/ml, was found to completely inhibit the generation of sC5b-9, and of C3a by two thirds; the binding of C3 and/or C3 fragments to the surface was almost entirely abolished. As a result of the inhibition of complement activation, the expression of CD11b on PMNs, and the binding of these cells to the biomaterial surface was almost completely lost. In contrast, the thrombin-antithrombin complexes, the platelet count, and the adherence of platelets to the surface, as reflected by the ATP binding and the release of beta-thromboglobulin, were not affected. These data show that complement activation, in association with extra-corporeal treatment, causes activation and binding of PMNs to the biomaterial and that these effects can be completely abolished by the addition of soluble recombinant sCR1.
authors.affiliation: Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Larsson
authors.forename: G
authors.initials: G
authors.lastname: Elgue
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.forename: K N
authors.initials: KN
authors.lastname: Ekdahl
authors.forename: U R
authors.initials: UR
authors.lastname: Nilsson
authors.forename: B
authors.initials: B
authors.lastname: Nilsson
mesh_terms: D001672:Biocompatible Materials; D001777:Blood Coagulation / Q000187:drug effects / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology; D002315:Cardiopulmonary Bypass; D003167:Complement Activation / Q000187:drug effects*; D015923:Complement C1r / Q000494:pharmacology*; D015926:Complement C3a / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D015938:Complement Membrane Attack Complex; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017452:Receptors, IgG; D011994:Recombinant Proteins; D015926:Complement C3a; D015923:Complement C1r